Back to Search Start Over

PurA is the main target of aurodox, a type III secretion system inhibitor.

Authors :
Yoshihiro Watanabe
Takeshi Haneda
Aoi Kimishima
Asaomi Kuwae
Takuya Suga
Takahiro Suzuki
Yoshiharu Iwabuchi
Masako Honsho
Sota Honma
Masato Iwatsuki
Hidehito Matsui
Hideaki Hanaki
Naoki Kanoh
Akio Abe
Yukihiro Asami
Satoshi Ōmura
Source :
Proceedings of the National Academy of Sciences of the United States of America; 4/23/2024, Vol. 121 Issue 17, p1-8, 17p
Publication Year :
2024

Abstract

Anti-microbial resistance (AMR) is one of the greatest threats to global health. The continual battle between the emergence of AMR and the development of drugs will be extremely difficult to stop as long as traditional anti-biotic approaches are taken. In order to overcome this impasse, we here focused on the type III secretion system (T3SS), which is highly conserved in many Gram-negative pathogenic bacteria. The T3SS is known to be indispensable in establishing disease processes but not essential for pathogen survival. Therefore, T3SS inhibitors may be innovative anti-infective agents that could dramatically reduce the evolutionary selective pressure on strains resistant to treatment. Based on this concept, we previously identified a polyketide natural product, aurodox (AD), as a specific T3SS inhibitor using our original screening system. However, despite its promise as a unique anti-infective drug of AD, the molecular target of AD has remained unclear. In this paper, using an innovative chemistry and genetic biology-based approach, we show that AD binds to adenylosuccinate synthase (PurA), which suppresses the production of the secreted proteins from T3SS, resulting in the expression of bacterial virulence both in vitro and in vivo experiments. Our findings illuminate the potential of PurA as a target of anti-infective drugs and vaccination and could open a avenue for application of PurA in the regulation of T3SS. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00278424
Volume :
121
Issue :
17
Database :
Complementary Index
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
176859989
Full Text :
https://doi.org/10.1073/pnas.2322363121